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Background: Dapiglutide, a dual glucagon-like peptide (GLP)-1 and GLP-2 receptor agonist, is under clinical development for bodyweight reduction in obesity, capitalising on GLP-1 receptor-mediated food intake-reducing effect leading to bodyweight loss and GLP-2 receptor-mediated improvement of gut barrier function and anti-inflammatory properties. Methods: ≥48 mmol/mol and recent ≥5% bodyweight change. The primary endpoint was percentage bodyweight change from baseline to week 12. The effects of 6 mg and 4 mg dapiglutide were tested hierarchically against first placebo, next each other in efficacy analyses with missing data replaced by standard multiple imputation. The study is registered with EU (trial no. 2022-501649-54-00) and ClinicalTrials.gov (NCT05788601). Findings: ) were randomised. In the primary efficacy analysis, 6 mg dapiglutide led to a mean bodyweight change of -2·1% 95% CI -4·3 to 0·2; p = 0·076 compared to placebo. Dapiglutide appeared safe and well-tolerated, with common adverse events including reduced appetite and nausea. No participants discontinued due to drug-induced adverse events, and in general, dropout rates were low, i.e. 0% (placebo), 11% (4 mg), and 6% (6 mg). Interpretation: Dapiglutide (4 mg or 6 mg) for 12 weeks did not result in a statistically significant difference in bodyweight change compared with placebo in persons with obesity. The safety profile was favourable, and the findings support further investigation of higher doses in larger and longer studies to evaluate the weight-lowering potential of dapiglutide. Funding: Unrestricted grant from Zealand Pharma.
Nielsen et al. (Sat,) studied this question.